POS1125 HYDROXYCHLOROQUINE USE IN PREGNANT WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND MAJOR CONGENITAL MALFORMATIONS IN THE OFFSPRING
Authors: N. V. Nguyen, E. Svenungsson, A. Dominicus, K. Hellgren, J. Simard, E. Arkema
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Hydroxychloroquine (HCQ) is currently recommended for all pregnant women with systemic lupus erythematosus (SLE) if tolerated. Some studies have reported an increased risk of malformations associated with HCQ, but others find no increased risk. <h3>Objectives</h3> To assess the risk of major congenital malformations (MCM) associated with exposure to HCQ during the 1st trimester in the offspring of women with SLE. <h3>Methods</h3> We conducted a population-based cohort study of pregnancies with a singleton birth from 2006 to 2020 among women with prevalent SLE in Sweden. Pregnancies were identified from the Medical Birth Register (MBR). Prevalent SLE was defined as having at least two ICD-coded visits in the National Patient Register before pregnancy, with at least one with an SLE specialist. The exposure was defined as filling at least one HCQ prescription during the 1st trimester (Prescribed Drug Register). The unexposed births were required to not have any HCQ dispensations from three months preconception to the end of the 1st trimester. The outcome was any ICD code for MCM in the offspring assessed at birth listed in the MBR, defined according to the European Surveillance of Congenital Anomalies classification. Inverse probability of treatment weighting (IPTW) using propensity score was applied to adjust for confounding. We included maternal characteristics, comorbidities (e.g., diabetes, other autoimmune diseases), and medication use (e.g., corticosteroids, other disease-modifying anti-rheumatic drugs) in the propensity score model as a priori variables. Risk ratios and 95% confidence intervals (RR 95%CI) were estimated using modified Poisson regression models in the weighted population with robust variance estimation. <h3>Results</h3> The study population comprised 407 exposed births and 520 unexposed births. The mothers' mean age at delivery was 32 (standard deviation ± 5). Overall, there were 21 births with at least one MCM, corresponding to an overall risk of 2.3%. The most common type of MCM was ventricular septal defect (n = 6). The unadjusted risks of MCM among the exposed and unexposed were 2.7% and 1.9%, respectively (unadjusted RR 1.42, 95%CI 0.60-3.28). The IPTW-adjusted population achieved a good balance across patient characteristics. The IPTW-adjusted RR was 1.59 (95%CI 0.67-3.75). The adjusted risk difference was 0.01 (95%CI -0.01-0.03). In a sensitivity analysis in which the exposure was defined as having at least one HCQ dispensation from three months preconception to the end of the 1st trimester, the IPTW-adjusted RR was 1.56 (95%CI 0.69-3.54). We could not examine different categories of HCQ daily dose due to very few events in each category. <h3>Conclusion</h3> In this birth cohort, our findings show an increased, but not statistically significant, risk of MCM at birth among births born to women with SLE exposed to HCQ during the 1st trimester compared to those without HCQ exposure. Our findings should be interpreted considering the lack of data on early pregnancy termination or loss induced by MCM. Future studies are warranted to investigate this association further and should utilize a longer follow-up for MCM ascertainment (i.e., within one year of birth). For managing SLE during pregnancy, the benefits of HCQ may still outweigh the risks. <h3>References</h3> [1]Diav-Citrin O, Blyakhman S, Shechtman S, Ornoy A. Pregnancy outcome following in utero exposure to hydroxychloroquine: a prospective comparative observational study. Reprod Toxicol Elmsford N. 2013 Aug;39:58–62. [2]Huybrechts KF, Bateman BT, Zhu Y, Straub L, Mogun H, Kim SC, et al. Hydroxychloroquine early in pregnancy and risk of birth defects. Am J Obstet Gynecol. 2021 Mar;224(3):290.e1-290.e22. [3]Howley MM, Werler MM, Fisher SC, Van Zutphen AR, Carmichael SL, Broussard CS, et al. Maternal exposure to hydroxychloroquine and birth defects. Birth Defects Res. 2021 Oct 15;113(17):1245–56. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Ngoc V. Nguyen: None declared, Elisabet Svenungsson Shareholder of: AstraZeneca and Pfizer, Speakers bureau: Janssen, Grant/research support from: Grant support from Merck, Annica Dominicus Shareholder of: AstraZeneca, Consultant of: AstraZeneca, Employee of: AstraZeneca, Karin Hellgren: None declared, Julia Simard: None declared, Elizabeth Arkema: None declared.